Editorial| Volume 59, ISSUE 1, 102703, February 2020

Foetal and neonatal alloimmune thrombocytopenia—A rare, potentially serious and often underdiagnosed bleeding condition

  • Jens Kjeldsen-Kragh
    Corresponding author at: University and Regional Laboratories, Region Skåne, Department of Clinical Immunology and Transfusion Medicine, Akutgatan 8, 22185, Lund, Sweden.
    Department of Laboratory Medicine, University Hospital of North Norway, Tromsø, Norway

    University and Regional Laboratories, Region Skåne, Lund, Sweden
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Published:December 31, 2019DOI:
      This theme issue of Transfusion and Apheresis Science has been devoted to foetal and neonatal alloimmune thrombocytopenia (FNAIT); the platelet counterpart of haemolytic disease of the foetus and newborn (HDFN). Whereas the alloantibodies in HDFN are directed against paternally inherited antigens on the foetus’ red blood cell, the alloantibodies in FNAIT are specific against foetal platelet antigens. The clinical presentations of FNAIT span a continuum from isolated thrombocytopenia over petechiae to severe internal bleedings of which intracranial haemorrhage (ICH) is one of the most feared complications. Most FNAIT-associated cases of ICH are caused by antibodies to human platelet antigen 1a (HPA-1a) and has been estimated to occur in around 1 in 10,000 unselected pregnancies.
      The contributors to this theme issue are from centres with long-standing interest in this rare disease. In the Netherlands clinical FNAIT management has been centralised to Leiden University Medical Center (LUMC) and the laboratory investigations are conducted at Sanquin, Amsterdam. Thus, the first contributions are from Thijs de Vos et al. from LUMC who give an introduction to the epidemiology and management of foetal and neonatal alloimmune thrombocytopenia and Leendert Porcelijn et al. from Sanquin reviewing recent progress and development of platelet antibody detection.
      Although FNAIT is considered as the platelet counterpart of HDFN there are still aspects of the disease pathogenesis that are not fully understood. Trude Victoria Rasmussen and Maria Therese Ahlen from the Norwegian National Unit for Platelet Immunology (NNUPI), Tromsø, Norway have provided a review on the various murine models that have been used for studying treatment, prevention and pathogenesis of FNAIT.
      For nearly 30 years it has been know that almost all HPA-1a-immunised women carry a particular HLA allele; HLA-DRB3*01:01. Jens Kjeldsen-Kragh from Dept. of Clinical immunology and Transfusion Medicine, Lund, Sweden and Maria Therese Ahlen from NNUPI, Tromsø have summarised more recent research regarding the immunological role of HLA-DRB3*01:01 and what impact this HLA allele has on immunisation risk and foetal/neonatal outcome.
      For HPA-1a-immunised pregnant women it is essential to determine the risk of having a foetus/newborn with FNAIT. If the father is heterozygous HPA-1a/b there is a 50 % chance that the foetus is HPA-1a negative, and in such a case the pregnant woman does not need to worry. In those cases where the father is heterozygous, it has been common practice to perform amniocentesis, expand the amnion cells and use DNA from these cells for foetal HPA-1a genotyping. Recently is has been possible to perform non-invasive foetal HPA-1a typing based on cell-free foetal DNA in mother’s plasma thereby eliminating the need of samples from the (presumed) father. Núria Nogués from the Blood and Tissue Bank of Catalonia, Barcelona, Spain present and discuss the various options for non-invasive foetal HPA-1a typing.
      Hitherto, the options have been limited to obstetric history when it comes to determining the risk of severe FNAIT if the HPA-1a-immunised woman is carrying an HPA-1a positive foetus. Within the last few years new interesting results have been published, which could be exploited for the development of new assays for risk stratification. Ulrich Sachs, Gießen, Germany have reviewed these new prospects for risk stratification of anti-HPA-1a alloimmunised pregnant women.
      Although intravenous immunoglobulin G (IVIg) has never been tested against placebo in a randomised clinical trial, most centres use IVIg off-label for treatment of HPA-1a-immunised pregnant women. Results from a number of observational studies have indicated that IVIg can reduce the risk of foetal/neonatal ICH in HPA-1a-immunised women, but how it works is still not clear. Hanna Wabnitz from St. Michael’s Hospital, Toronto, Canada take us through the different mechanism that could explain how IVIg works.
      For more than two decades the FNAIT management strategy in Norway has differed from most other countries, as IVIg is only rarely used. Heidi Tiller et al. from the University Hospital of North Norway, Tromsø, Norway present the Norwegian FNAIT management strategy and explain and discuss why this strategy has been chosen.
      After anti-D was introduced around 50 ago for the prevention of anti-RhD-associated HDFN, this condition has almost been eradicated. Hence, RhD immunoprophylaxis can be considered as one the most successful immunological intervention in clinical medicine. A similar hyperimmune anti-HPA-1a IgG for the prevention of HPA-1a-immunisation and FNAIT has been developed by the EU-funded PROFNAIT Consortium. Mette Kjær from the University Hospital of North Norway, Tromsø and Finnmark Hospital Trust, Hammerfest, Norway, together med collaborators within and outside the PROFNAIT Consortium discuss strategies to develop this new drug for the prevention of HPA-1a immunisation and FNAIT.
      The voice of the affected children and families are rarely heard in the scientific literature. For this reason, Thea Palmer, Founder and Chair of Naitbabies has been invited to present their charitable organisation. Naitbabies was founded in 2011 and is a patient organisation for families affected by FNAIT. Since its establishment, it has already past 1000 members, primarily from English-speaking countries but also from Scandinavia and Germany. Physician and other health personnel involved in FNAIT management should make parents aware of this organisation because they can provide a type of support that is not available within the health care system.
      It is my hope that the palette of papers in this theme issue can provide you with up-to-date knowledge within some of the most burning topics related to FNAIT. Enjoy your reading!


      Jens Kjeldsen-Kragh obtained his medical degree from Aarhus University, Denmark and his PhD from the University of Oslo, Norway. After his residency (Immunology and Transfusion Medicine) he worked a number of years as a Senior Consultant Physician/Professor at Oslo University Hospital. He was one of the founders of the Norwegian biotech company Prophylix AS in which he functioned as Chief Scientific Officer. Together with colleagues from the University Hospital of North Norway he initiated the establishment of the EU-funded PROFNAIT Consortium which aimed at developing a prophylactic treatment for the prevention of HPA-1a-immunisation and foetal and neonatal alloimmune thrombocytopenia. He currently holds a position as Senior Consultant Physician at the Department of Clinical Immunology and Transfusion Medicine, Lund, Sweden.